Facile hyperpolarization chemistry for molecular imaging and metabolic tracking of [1-13C]pyruvate in vivo


Hyperpolarization chemistry based on reversible exchange of parahydrogen, also known as Signal Amplification By Reversible Exchange (SABRE), is a particularly simple approach to attain high levels of nuclear spin hyperpolarization, which can enhance NMR and MRI signals by many orders of magnitude. SABRE has received significant attention in the scientific community since its inception because of its relative experimental simplicity and its broad applicability to a wide range of molecules, however in vivo detection of molecular probes hyperpolarized by SABRE has remained elusive. Here we describe the first demonstration of SABRE-hyperpolarized contrast detected in vivo, specifically using hyperpolarized [1-13C]pyruvate. A biocompatible formulation of hyperpolarized [1-13C]pyruvate was injected into healthy Sprague Dawley and Wistar rats, and metabolic conversion of pyruvate to lactate, alanine, pyruvate-hydrate, and bicarbonate was detected. Measurements were performed on the liver and kidney at 4.7 T via time-resolved spectroscopy and chemical-shift-resolved MRI. In addition, whole-body metabolic measurements were obtained using a cryogen-free 1.5 T MRI system, illustrating the utility of combining lower-cost MRI systems with simple, low-cost hyperpolarization chemistry to develop scalable, next-generation molecular imaging.